Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2024; 16(5): 2123-2140
Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.2123
MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1- extracellular signal-regulated kinase-1/2 axis
Hong-Xia Bai, Xue-Mei Qiu, Chun-Hong Xu, Jian-Qiang Guo
Hong-Xia Bai, Jian-Qiang Guo, Department of Gastroenterology, The Second Hospital of Shandong University, Jinan 250000, Shandong Province, China
Hong-Xia Bai, Chun-Hong Xu, Department of Gastroenterology, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, China
Xue-Mei Qiu, Department of Reproductive Center, Zaozhuang Maternal and Child Health Care Hospital, Zaozhuang 277000, Shandong Province, China
Author contributions: Bai HX and Qiu XM prepared material, data collection, analysis, and performed were design; Xu CH collected the samples; Bai HX and Xu CH performed animal experiments; Bai HX and Guo JQ wrote the manuscript. All authors read and approved the final manuscript. All authors contributed to the study’s conception and design.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Liaocheng People's Hospital.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Liaocheng People's Hospital.
Informed consent statement: Written informed consent was obtained from all study participants, or their legal guardian included in this study.
Conflict-of-interest statement: The author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.
Data sharing statement: The authors confirm that the data supporting the findings of this study are available within the article.
ARRIVE guidelines statement: All the authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jian-Qiang Guo, MD, PhD, Chief Physician, Director, Senior Researcher, Department of Gastroenterology, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Tianqiao District, Jinan 250000, Shandong Province, China. guo_jianqiang@126.com
Received: January 11, 2024
Peer-review started: January 11, 2024
First decision: January 30, 2024
Revised: February 19, 2024
Accepted: March 13, 2024
Article in press: March 13, 2024
Published online: May 15, 2024
Processing time: 118 Days and 22.3 Hours
Abstract
BACKGROUND

MicroRNAs (miRNAs) regulate gene expression and play a critical role in cancer physiology. However, there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer (GC).

AIM

To investigate the role and molecular mechanism of miRNA-145-5p (miR145-5p) in the progression of GC.

METHODS

Real-time polymerase chain reaction (RT-PCR) was used to detect miRNA expression in human GC tissues and cells. The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays, respectively. Cell proliferation was measured using cell counting kit-8 and colony formation assays, and apoptosis was evaluated using flow cytometry. Expression of the epithelial-mesenchymal transition (EMT)-associated protein was determined by Western blot. Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system. Serpin family E member 1 (SERPINE1) expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining. The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis. The association between SERPINE1 and GC progression was also tested. A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p. The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.

RESULTS

GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA. Overexpression of miR-145-5p was associated with decreased GC cell proliferation, invasion, migration, and EMT, and these effects were reversed by forcing SERPINE1 expression. Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression. Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2 (ERK1/2).

CONCLUSION

This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC. MiR-145-5p was found to affect GC cell proliferation, migration, and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

Keywords: Gastric cancer; MicroRNA-145-5p; Serpin family E member 1; Epithelial-mesenchymal transition; Proliferation; Extracellular signal-regulated kinase-1/2

Core Tip: Abnormal microRNAs (miRNAs) expression is found in multiple diseases, including cancer, where it contributes to tumor progression. The exact role of miRNA-145-5p (miR-145-5p) in gastric cancer (GC) remains poorly understood. The current study assessed the molecular pathways used by miR-145-5p to regulate GC in tumor tissues, cell lines, and a nude mouse model. MiR-145-5p was shown to target serpin family E member 1, regulate the extracellular signal-regulated kinase-1/2 pathway, and directly impact GC progression, playing an important role in this disease. The findings identify the molecular mechanism of GC progression.